Nanofibers are thin small fibers, with typical diameters ranging from tens to hundreds of nanometers, up to about 1 micrometer. Nanofibers have been formed from polymers, carbon, and ceramic. Nanofibers have attracted great interest because of their extraordinarily high surface area and length-to-width ratio, as well as their unique physical and mechanical properties. Nanofibers are being used in such areas as filtration, fiber-reinforced nanocomposites, wound dressing, drug delivery, artificial organs, micro-electrical systems, and micro-optical systems. However, fabrication of nanofibers is very challenging due to their minute diameters. Traditional methods, such as formation in porous solids or at the step-edges of laminated crystals, are often ineffective and costly. An alternative method is electrostatic fiber formation or electrospinning. Electrospinning is a relatively simple and versatile method.
In electrospinning, a high voltage (e.g., ˜3 to ˜50 kV) is applied between a target (or collector) and a conducting capillary into which a polymer solution or melt is injected. The high voltage can also be applied to the solution or melt through a wire if the capillary is a nonconductor such as a glass pipette. The collector may be a metal plate or screen, a rotating drum, or even a liquid bath if the capillary is vertical. Initially the solution at the open tip of the capillary is pulled into a conical shape (the so-called “Taylor cone”) through the interplay of electrical force and surface tension. At a certain voltage range, a fine jet of polymer solution (or melt) forms at the tip of the Taylor cone and shoots toward the target. Forces from the electric field accelerate and stretch the jet. This stretching, together with evaporation of solvent molecules, causes the jet diameter to become smaller. As the jet diameter decreases, the charge density increases until electrostatic forces within the polymer overcome the cohesive forces holding the jet together (e.g., surface tension), causing the jet to split or “splay” into a multifilament of polymer fibers. The fibers continue to splay until they reach the collector, where they are collected as nonwoven fibers, and are optionally dried. The diameter of an electrospun nanofiber is typically between about 50 nm and about 5 μm. High-speed photographic studies have suggested that, at least in some cases, what had appeared to be a multifilament was in fact a single, ultrafine fiber, being whipped very rapidly.
A wide variety of polymers have been electrospun from solutions and melts. A large number of papers describing the electrospinning process have been published, particularly in the past decade. Two recent review articles summarizing the state of the art are A. Frenot et al., “Polymer nanofibers assembled by electrospinning,” Current Opinion in Colloid and Interface Science, vol. 8, pp. 64-75 (2003); and Z. Huang et al., “A review on polymer nanofibers by electrospinning and their applications in nanocomposites,” Composites Science and Technology, vol. 63, pp. 2223-2253 (2003).
Baker D A, Brown P J. Reactive routes to making modified nanofiber structures via electrospinning. Polymer Preprints (2003), 44(2), 118-119 reported the addition of azides to polymer solutions prior to electrospinning. The azides could react, crosslink, functionalize, and covalently bind polymer chains. Electrospinning mixtures of polymers with the additives could be used for the covalent binding of synthetic polymers with natural polymers in a single manufacturing step. It was said that applying heat or UV light during electrospinning was said to modify nanofiber substrates either during the fiber formation process or by post-spin treatments; however, the only successful experimental results reported were apparently for post-spin reaction and cross-linking. The experimental procedures reported the preparation of solutions containing polymer and azide crosslinking agents. The solutions were then weighed, sealed, and checked for solvent loss during the time taken for dissolution. After an unspecified lapse of time, the solutions were later used in electrospinning procedures. The reaction and crosslinking in these experiments apparently did not take place until a post-spinning thermal analysis step.
Cross-linked polymers, hydrogels, hyperbranched polymers, and dendrimers have properties that differ from those of otherwise-comparable linear polymers. For example, they often have higher chemical stability and improved mechanical properties. They often possess unique chemical properties and functionalities. Such polymers have been used in diverse applications including coatings, composite resins, controlled drug release, organic-inorganic hybrid materials, solid supports for catalysts, and supports for chromatography or ion-exchange resins. However, highly cross-linked polymers and hyperbranched polymers are generally difficult to form as fibers through prior techniques, and even more difficult to form into nanofibers, because they typically have low solubility, and they typically will not melt without undergoing heat-induced decomposition, due to the strong intermolecular bonding or entanglement of the polymer molecules and the formation of polymer networks.
Ding, B. et al, “Preparation and characterization of a nanoscale poly(vinyl alcohol) fiber aggregate produced by an electrospinning method,” J. Poly. Sci. B: Poly. Phys., (2002), 40, 1261-1268, reported the preparation of crosslinked poly(vinyl alcohol) (PVA) nanofibers (100-500 nm) by first mixing 0˜10% glyoxal (a crosslinking agent) and phosphoric acid (as a catalyst) with a 10% PVA-water solution, then electrospinning the mixed solution at room temperature, followed by post-spinning thermal curing of the electrospun-PVA fiber in an oven at 120° C. for 5 min. It was reported that the crosslinked PVA fiber aggregates were more hydrophobic, and that they exhibited better mechanical properties.
U.S. Pat. No. 6,382,526 discloses a process for forming nanofibers by comprising the steps of feeding a fiber-forming material into an annular column, the column having an exit orifice, directing the fiber-forming material into a gas jet space, thereby forming an annular film of fiber-forming material, the annular film having an inner circumference, simultaneously forcing gas through a gas column, which is concentrically positioned within the annular column, and into the gas jet space, thereby causing the gas to contact the inner circumference of the annular film, and ejects the fiber-forming material from the exit orifice of the annular column in the form of a plurality of strands of fiber-forming material that solidify and form nanofibers having a diameter up to about 3,000 nanometers.
U.S. Pat. No. 6,520,425 discloses a nozzle for forming nanofibers by using a pressurized gas stream comprising a center tube, a first supply tube that is positioned concentrically around and apart from the center tube, a middle gas tube positioned concentrically around and apart from the first supply tube, and a second supply rube positioned concentrically around and apart from the middle gas tube. The center tube and first supply tube form a first annular column. The middle gas tube and the first supply tube form a second annular column. The middle gas tube and second supply tube form a third annular column. The tubes are positioned so that first and second gas jet spaces are created between the lower ends of the center tube and first supply tube, and the middle gas tube and second supply tube, respectively.
U.S. Pat. No. 6,308,509 discloses nanofibers having a diameter ranging from about 4 to 1 nm, and a nano denier of about 10−9. The use of the electro-spinning process permits production of the desired nanofibrils. These fibrils in combination with a carrier or strengthening fibers/filaments can be converted directly into nonwoven fibrous assemblies or converted into linear assemblies (yarns) before weaving, braiding or knitting into 2-dimensional and 3-dimensional fabrics. The electrospun fiber can be fed in an air vortex spinning apparatus developed to form a linear fibrous assembly. The process makes use of an air stream in a properly confined cavity. The vortex of air provides a gentle means to convert a mixture of the fibril fed directly or indirectly from the ESP unit and a fiber mass or filament into an integral assembly with proper level of orientation. Incorporation of thus produced woven products into tissue engineering is part of the present invention.
Published international patent application WO 01/27365 discloses a fiber comprising a substantially homogeneous mixture of a hydrophilic polymer and a polymer that is at least weakly hydrophobic. The fiber optionally contains a pH adjusting compound. A method of making the fiber is disclosed, electrospinning fibers of the substantially homogeneous polymer solution. The fibers are disclosed as having application for dressing wounds.
Recently, submicron fibers and nanofibers of ceramic oxides, such as silica and alumina-borate have been reported using a sol-gel process and electrospinning. See C. Shao et al., “A novel method for making silica nanofibres by using electrospun fibres of polyvinylalcohol/silica composite as precursor,” Nanotechnology, vol. 13, pp. 635-637 (2002); and H. Dai et al., “A novel method for preparing ultra-fine alumina-borate oxide fibres via an electrospinning technique,” Nanotechnology, vol. 13, pp. 674-677 (2002). A typical process includes (1) acid hydrolysis of organometallic precursors such as tetraethyloxysilane (TEOS) to form a colloid solution (sol), (2) mixing the sol with an aqueous or alcohol solution of a polymer such as polyvinyl alcohol (PVA), and digesting to form a viscous sol; (3) electrospinning the sol to form a silica/PVA composite gel fiber; (4) calcination or sintering the gel fiber to yield a porous silica or alumina fiber. TiO2 and SnO2 nanofibers have been prepared by electrospinning a titanium tetraisopropoxide (Ti(OiPr)4)/poly(vinyl pyrrolidone)(PVP) solution, or a tin (IV) tetraisopropoxide (Sn(OiPr)4) / PVP / ethanol solution, followed by rapid hydrolysis by moisture in air, and calcination. See D. Li et al., “Fabrication of titania nanofibers by electrospinning,” Nano Letters, vol. 3, pp. 555-560 (2003); and D. Li et al., “Electrospinning of polymeric and ceramic nanofibers as uniaxially aligned arrays,” Nano Letters, vol. 3, pp. 1167-1171 (2003). Because the composite gel fibers produced by these processes have contained high levels of organic polymers (typically, about 30% to 66% PVA or PVP), removal of the polymer by calcination has left substantial voids in the final ceramic nanofibers, voids that cannot be healed by calcination or sintering. Such porous ceramic oxide nanofibers have a large-surface area, and may be used in catalysts, filtration, or absorbents. However, they are not well-suited for use as reinforcing elements due to their poor mechanical properties.
Bioactive materials, such as bioactive glass, hydroxyapatite, and glass-ceramic A-W can react with biological fluids, and can bond directly to living bone. They have been used in orthopedic and dental implants and cements. However, such materials have had low fracture toughness. Zirconia and titania ceramics have been used to reinforce the bioactive materials. See T. Kasuga et al., “Bioactive glass-ceramic composite toughened by tetragonal zirconia,” pp. 137-142 in Yamamuro et al. (Eds.), CRC Handbook of Bioactive Ceramics, Volume 1 (1990); and Kokubo et al, “Novel bioactive materials with different mechanical properties,” Biomaterials, vol. 24, pp. 2161-2175 (2003). To the inventor's knowledge, however, zirconia-reinforced bioactive glass-ceramic nanofibers or zirconia nanofiber-reinforced bioactive glass-ceramics have not previously been reported.
The fabrication of α-alumina nanofibers by sol-gel chemistry and electrospinning was reported by G. Larsen et al., “A method for making inorganic and hybrid (organic/inorganic) fibers and vesicles with diameters in the submicrometer and micrometer range via sol-gel chemistry and electrically forced liquid jets,” J. Am. Chem. Soc., vol. 125, pp. 1154-1155 (2003).
Zirconia-based ceramics have superior properties such chemical resistance, thermal stability, high mechanical strength and toughness, high ionic conductivity, and catalytic properties. Zirconia has been widely used in engineering and technological applications. In recent years, zirconia-based ceramics have gained popularity in medical devices and dentistry because of their excellent esthetics, biocompatibility, and high toughness. Zirconia particles and nanoparticles have been used as fillers in dental composites to increase both radiopacity and resistance to hydrolytic degradation. There is an unfilled need for dense ZrO2—SiO2 and ZrO2—Y2O3 nanofibers for use as reinforcement fillers in dental composites. Zirconia-based ceramic nanofibers will significantly increase the mechanical strength and fracture toughness of dental composites, while satisfying the stringent requirements for color and translucency needed for such- purposes. Current commercially available zirconia fibers are too thick for such applications (5˜10 μm), because their resulting composites are highly opaque.
To the knowledge of the inventor, continuous, dense zirconia-based nanofibers have not previously been reported. Nor have there been prior reports of any method for the direct fabrication of dense ceramic nanofibers through precursor gel nanofibers by electrospinning, without the incorporation of a significant amount of organic polymer.
The production of continuous nanofibers by electrospinning requires polymers (or other macromolecules) in the form of a solution or melt. A solution or suspension of discrete small molecules, including, e.g., monomers, oligomers, colloids, or nanoparticles, cannot ordinarily be electrospun into a continuous nanofiber, but instead through an electrospray will produce droplets or nanoparticles. There is an unfilled need for a method to make continuous, cross-linked or hyperbranched polymer nanofibers, including crosslinked hydrogel nanofibers. There is an unfilled need for a method to modify the chemical or physical properties of polymers in nanofibers to yield cross-linked polymer nanofibers and other nanofiber materials that are difficult or impossible to make by existing techniques. To the inventor's knowledge, no prior work has reported the successful production of nanofibers or crosslinked nanofibers by electrospinning, in which polymerization or cross-linking reactions occur during or immediately prior to the electrospinning itself, as opposed to reactions that have occurred substantially before or substantially after the electrospinning process.